Transcript NEW ANTICOAGULANTS

Mechanical Clot Detection
Stago’s Viscosity-based Clot
Detection System
Viscosity based Detection System
Viscosity based Detection System
Viscosity based Detection System
Viscosity based Detection System
Viscosity based Detection System
NEW ANTICOAGULANTS
Katy Whelchel MT(ASCP)SH
Diagnostica Stago, Inc.
Technical Support Specialist
February 23, 2006
Maintain hemostatic balance
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the body must maintain a fluid
equilibrium
need to maintain balance between
bleeding & clotting
vessels
“Coagulation”
Proteins
Platelets
Fibrinolysis/ Inhibitors
ANTICOAGULANT THERAPY
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Decrease the risk of post-op thrombosis
Decrease the risk of thrombosis in
patients with risk factors
Decrease the risk of spontaneous
abortions in patients with AntiPhospholipid Syndrome (APS) - lupus
anticoagulants
STANDARD ANTICOAGULANTS
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HEPARIN (UFH)
COUMADIN (warfarin)
UFH – a few things to remember
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Will affect PTT- how much depends
dosing and your reagent system
Easily monitored (accurately!) with the
Anti-Xa method
Can be used in patients with renal
failure
HAS an antidote (protamine sulfate)
Coumadin –a few things to remember
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Can be monitored by the PT/INR
Can be given long term for high risk
patients
Can be used in patients with renal
failure
HAS an antidote (Vitamin K)
St. Lucia Island flowers
2 classes of NEW
ANTICOAGULANTS
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Antithrombin Dependant
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LMWH – Lovenox, Fragmin, Innohep
(tinzaparin – has been used on CAP surveys)
DANAPROID (not available in US)
FONDAPARINUX (Arixstra)
Direct Thrombin Inhibitors
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HIRUDEN – LEPIRUDEN (Refludan)
ARGATROBAN (Novastan)
Bivalirudin
Ximelagatran- the “new” coumadin
Why do we care about these new
anticoagulants??
They are advertised
as “no monitoring
needed”!
Why do we care about these new
anticoagulants??
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They can and DO interfere with our current
coagulation tests
Can you say how much of this new drug is in
the patient’s system?
What do you do for these patients?
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Patient is bleeding
Patient is clotting – despite therapy
Pre-op assessment?
PT and PTT may or may not be “normal”
Why do we care about these new
anticoagulants??
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Special patient populations need special
consideration:
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Pregnancy
Renal dysfunction
Liver dysfunction
Anorexic or morbidly obese patients
Heparins
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UFH work on the activated factors
LMWHs work where the extrinsic and
intrinsic factors come together with
Factor Xa
Both use the patient’s ATIII to work
Coag Cascade
LMWH Action
LMWH HEPARINS
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LMWH – better bioavalibility than UFH
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Created from UFH
Since it’s a smaller molecule it can be
administered as a subcutaneous injection – given
in fixed doses for MOST patients
Therapeutic Ranges:
0.5 – 1.1 (2 injections/day)
1.0 – 2.0 (1 injection/ day)
Timing of specimens - peak at about 4 hours
after sub Q injection
Heparin Family picture
LMWH HEPARIN
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Doesn’t change the APTT (much) – an
increased APTT may signify an overdose
of LMWH or some other influence on
the APTT (platelet antibodies)
Difficult to reverse with protamine
sulfate (antidote for UFH)
Cleared through the kidneys
LMWH HEPARIN
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LMWH available in the US:
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Enoxaparin (Lovenox): prevent DVT/PE
around surgery, treat DVT/PE, unstable
angina
Dalteparin (Fragmin): prevent and treat
DVT/PE, treat unstable angina
Tinzaparin(Innohep): treat DVT/PE
Who should be monitored for
LMWH?
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Patients with kidney problems
(need to check creatinine
clearance)
Patients that are obese or have a
very low body weight
Children, burn patients
How should LMWH be
monitored?
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Monitor with an anti-Xa method,
using LMWH calibrators and
controls.
Samples should be drawn 4 hours
after dosing.
Marigot Bay, St. Lucia
Danaproid, Fonduparinux
DANAPROID
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(not available in the US)
Mixture of heparinoids
Usually given to HIT patients
Works through antithrombin to inhibit factor
Xa (little effect on other factors)
Administered twice a day – IV or Sub Q
Therapeutic ranges – IV=0.5 – 0.8 Sub Q=
0.13-0.35
Monitored by anti-Xa (like LMWH) – using
danaproid as the calibrator.
Danaproid (cont’d)
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It may prolong the PTT,as well as affect
the PT, TT and ACT.
Used successfully in HIT – however,
platelet count should be monitored.
No agent that will reverse the effects of
the drug.
FONDAPARINUX (Arixtra)
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Synthetic pentasaccharide – accelerates the
binding of AT to Xa – the “ultimate LMWH”
Pure anti-Xa effect
Commonly used to prevent VTE in orthopedic
surgery
Administered Sub Q
Half-life of 13 – 15 hours, so only 1 dose per
day.
Excreted through kidney (check creatinine
clearance…..)
Fondaparinux (cont’d)
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PT and PTT are relatively insensitive to this
drug, but may be slightly prolonged.
Low bleeding incidence.
Has not been shown to cause HIT
No direct inhibitor for Arixtra which can
reverse it’s anticoagulant effect.
May be monitored by an Anti-Xa method
using the drug as a calibrator.
Fondaparinux (cont’d)
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Remember – there is no antidote. So if
the patient has too much “on board”,
the PT and PTT may be normal, but
they may still be bleeding…….can use
Factor VIIa concentrate (novoseven) or
activated prothrombin concentrates to
reverse effect.
Ship: The Brig Unicorn
DIRECT THROMBIN
INHIBITORS
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Hirudin – Lepirudin (Refludan)
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Hirudin: Medicinal Leech
Refludan: recombinant polypeptide with same
action
Agatroban
Bivalirudin (Angiomax)
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Do not cause thrombocytopenia; used successfully
with HIT
Directly blocks Thrombin
Administered by IV or Sub Q
REQUIRES MONITORING
Direct Thrombin Inhibitors
DIRECT THROMBIN
INHIBITORS
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These drugs have a very short half life.
Agatroban cleared by the liver
Lepirudin is cleared by the kidneys.
Bivalirudin is cleared by the kidneys
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Have to be aware of these factors with the
patient!
ARGATROBAN
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Derivative of amino acid arginine
Directly binds to Thrombin
Metabolized by the liver, and excreted
through the kidney – so can be an alternate
for patients with renal disease.
Must be monitored by APTT (can also be
monitored by the ACT). Therapeutic range is
1.5-3.0 x Baseline APTT.
REFLUDAN - Lepirudin
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APTT – IV=1.5 – 3.0 x patient baseline
Sub Q= 2.2 – 2.7 X baseline APTT
(specimen drawn 3 hours after administration)
HOWEVER, APTT reagents vary in their sensitivity to
Refludin
ECARIN CLOTTING TIME (used in some facilities)
CHROMOGENIC ASSAY BASED ON THROMBIN
INHIBITION (developed for research only at this
point) – most accurate assay
DIRECT THROMBIN
INHIBITORS
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These drugs will affect the PT/INR – since they work
at the bottom of the cascade
Lepirudin: recommend stopping drug once INR>2.0
Agatroban: recommend stopping drug once INR>4.0
Levels are PT reagent dependent!! Literature says
that reagents with a lower ISI have less variability in
reactivity. Higher ISI reagents have greater variablity
in response.
Will affect results if patient is also on Coumadin!
DIRECT THROMBIN
INHIBITORS
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Since these drugs affect the PT/INR
system – and since they have a very
short half-life – the good news is that if
they are discontinued for a couple of
hours, the PT should return to normal.
The bad news is that the kidneys and
liver have to be working for this to
happen.
Bivalirudin
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Approved for use in the cardiac cath lab
Bivalent thrombin inhibitor
Short half-life (20 -30 min)
Exclude patients with creatinine >3.0
Live Volcano, St. Lucia
DIRECT THROMBIN
INHIBITORS
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Ximelagatran – the “new Coumadin”
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Oral tablet
Direct thrombin inhibitor
Converts to melagatran in the stomach
Cleared by kidneys
Irreversible – factor VII concentrate
recommended for severe hemorrhage
DIRECT THROMBIN
INHIBITORS
Ximelagatran – the “new Coumadin” (cont’d)
 it’s supposed to work better than our current
LMWHs in preventing DVTs in people who
have had hip surgery
 Theoretically: NO MONITORING! It doesn’t
matter how old you are, how much you
weigh, etc. it is supposed to be
safe…..however it causes liver damage in 610% of patients who take it long term. And
remember – it is cleared by the kidneys.
DIRECT THROMBIN
INHIBITORS
Ximelagatran – the “new Coumadin” (cont’d)
 Not approved by FDA – yet.
 If you were going to monitor Ximelagatran,
remember it is a thrombin inhibitor – so you’d
have to monitor the APTT – NOT a PT even
though it is the “new Coumadin”!!
 APTT’s response again will be variable
depending on reagent system.
DIRECT THROMBIN
INHIBITORS
Ximelagatran – the “new Coumadin”
(cont’d)
 So – for the time being, we’ll still be
doing PT/INR for coumadin therapy.
Summary
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Many of these anticoagulants are currently in use.
They may affect routine and specialty coagulation
tests – remember where they affect the cascade!
If abnormal results are obtained, and not expected –
ask what drugs the patient is on.
Remember many will act differently if the patient has
renal or hepatic impairment.
The “tried and true” may still be the easiest to use if
monitored correctly.
St. Lucia Sunset
The end.